Predictors and outcomes of intracranial hemorrhage in 58,000 patients with atrial fibrillation on oral anticoagulation: insights from COMBINE-AF
Bibliographic record
Abstract
Abstract Background Among anticoagulated patients with atrial fibrillation (AF), intracranial hemorrhage (ICH) is the leading cause of bleeding-related death and disability. The COMBINE-AF database has patient-level data from four major randomized-controlled trials [ROCKET-AF (rivaroxaban), RE-LY (dabigatran), ENGAGE-TIMI 48 (edoxaban), ARISTOTLE (apixaban)] of direct oral anticoagulants (DOACs) versus warfarin in patients with AF. Purpose/Methods We investigated the rates, predictors, and mortality of ICH in patients randomized to DOAC (rivaroxaban, dabigatran, edoxaban, apixaban) or warfarin. ICH was subclassified as subdural or non-subdural (intracerebral, intraventricular, subarachnoid, epidural). Multivariable Cox models were used to identify predictors of ICH. Frequencies and fatality rates of ICH were calculated and displayed as Kaplan-Meier curves. Results In COMBINE-AF, there were 58,634 patients randomized to either DOAC (n=29,362) or warfarin (n=29,272). The mean age was 70.5 years, 37% were female, and 81% were White. The mean CHA2DS2-VASc score was 2.6, 43% of patients had a history of smoking, 31% had diabetes, and 29% had prior stroke/TIA. After a mean of 32 months, ICH occurred in 593 patients (1.01%, 0.58 per 100-patient years, 95% CI [0.54, 0.63]). The most significant independent predictors of ICH in order of importance were: treatment with warfarin, older age, prior stroke/TIA, enrollment in Asia, antiplatelet use at randomization, and history/risk of falls (Figure 1). Mortality after ICH was 48.4% (287/593 participants), with a majority of deaths (82%) occurring within 30 days of ICH event. Non-subdural ICH was more common than subdural ICH (73% vs 25%) and had a higher risk of death (Figure 2). Participants randomized to DOAC had a lower risk of both subdural and non-subdural ICH than those treated with warfarin; however, mortality rates after ICH were similar regardless of anticoagulant type. Conclusion ICH is an uncommon but devastating complication of oral anticoagulation in patients with atrial fibrillation. The mortality rate following ICH is high, particularly following non-subdural ICH. To reduce the risk of ICH, clinicians should consider using DOACs over warfarin and carefully evaluate the need for antiplatelet therapy, particularly in patients with other significant predictors of ICH such as prior stroke, advanced age, residence in Asia, and history of falls.Predictors of Intracranial Hemorrhage90-Day Mortality after ICH
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".